Beales P E, Williams A, Krug J, Signore A, Chianelli M, Andreani D, Pozzilli P
Department of Diabetes and Metabolism, St Bartholomew's Hospital, London, UK.
Diabete Metab. 1992 Jan-Feb;18(1):48-53.
Tenidap, a novel compound inhibiting cyclooxygenase and lipoxygenase, also possessing an inhibitory effect on interleukin-1 secretion by in vitro activated macrophages, has been administered to the non obese diabetic (NOD) mouse to evaluate its action on the induction and progression of insulitis and the diabetes incidence. Animals were allocated to three groups (group A: control group; group B: 12 mg/kg/day Tenidap; group C: 36 mg/kg/day Tenidap); female animals only were followed up to investigate the effect on diabetes incidence. The administration of Tenidap influenced the natural course of insulitis in male NOD mice; thus, at 60 and 100 days of age the mean percentage of infiltrated islets was significantly reduced compared to control animals (p less than 0.02). Moreover the severity of lymphocytic infiltration at 60 days of age was reduced in male mice of group B and C compared to control mice (p less than 0.004 and p less than 0.0001, respectively) whereas at 100 days of age this difference was not significant. However the progression towards severe insulitis in male animals receiving Tenidap was halted compared to control animals. Tenidap had also a significant dose dependent effect at 60 days on the severity of lymphocytic infiltration (group B vs. group C, p less than 0.01). By contrast, this agent had no effect on the degree of insulitis and diabetes incidence in female NOD mice. In both sexes at the end of follow-up a significant reduction in body weight was observed in animals of Group C compared to control animals (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
替硝唑,一种新型的抑制环氧化酶和脂氧化酶的化合物,对体外活化的巨噬细胞分泌白细胞介素-1也有抑制作用,已被用于非肥胖糖尿病(NOD)小鼠,以评估其对胰岛炎的诱导和进展以及糖尿病发病率的影响。动物被分为三组(A组:对照组;B组:12毫克/千克/天替硝唑;C组:36毫克/千克/天替硝唑);仅对雌性动物进行随访以研究对糖尿病发病率的影响。替硝唑的给药影响了雄性NOD小鼠胰岛炎的自然病程;因此,与对照动物相比,在60和100日龄时,浸润胰岛的平均百分比显著降低(p小于0.02)。此外,与对照小鼠相比,B组和C组雄性小鼠在60日龄时淋巴细胞浸润的严重程度降低(分别为p小于0.004和p小于0.0001),而在100日龄时这种差异不显著。然而,与对照动物相比,接受替硝唑的雄性动物向严重胰岛炎的进展被阻止。替硝唑在60天时对淋巴细胞浸润的严重程度也有显著的剂量依赖性效应(B组与C组相比,p小于0.01)。相比之下,该药物对雌性NOD小鼠的胰岛炎程度和糖尿病发病率没有影响。在随访结束时,与对照动物相比,C组动物无论雌雄体重均显著降低(p小于0.002)。(摘要截短于250字)